AIDS is the leading cause of death among adolescents in Africa, and the 2nd leading cause of death among adolescents globally, with two-thirds of all new HIV infections amongst 15-19 year olds occurring in adolescent girls. Orphaned and separated children (OSC) are at especially high risk of becoming HIV infected. ?Positive Outcomes for Orphans (POFO): HIV Risk as Young Adults? will evaluate factors associated with HIV risk, HIV testing, and HIV treatment engagement and retention during adolescence and young adulthood. Between 2006-8, the HIV/AIDS and Orphan Care: Positive Outcomes for Orphans (POFO) study used random sampling survey methods to enroll 3,057 OSC ages 6-12 living in families (N=1,562) and institutional care settings (N=1,495) representative of the OSC populations in 5 culturally, economically, and politically distinct countries: Ethiopia, Kenya, Tanzania, Cambodia and India. With 10 years of follow-up, POFO is the only multi-country longitudinal study of OSC and its findings have directly impacted policies and interventions for OSC. Half of all adolescents living with HIV are in 6 countries, 4 of which were included in this study. To date, 9% of POFO participants (now ages 16-22) have tested, or are suspected to be, HIV positive, a rate well above national averages. The first aim of this grant is to follow the POFO OSC cohort as they transition through adolescence and into young adulthood to identify associations with HIV risk and related behaviors. With three additional rounds of data collection, up to 14 years of data will be available for each OSC participant (ages 21-27 at study completion). HIV testing will be offered at each round and barriers and facilitators of treatment engagement and retention will be assessed. The second aim is to create long- term predictive models of HIV-relevant outcomes that identify in early childhood those OSC who are at highest risk for HIV as young adults. All 14 years of data will be used to develop models to support the development of screening tools that identify high-risk OSC early in life. In order to derive weights that allow estimates to represent today?s OSC, we will compare the original POFO sample with a new sample of OSC from the same areas: we will add a new cross-sectional sample of 250 OSC ages 6-16 (to match POFO I and II) at each of the four sites participating in this study (N=1,000) following the original POFO I sampling procedures. The third aim is to identify site- and gender-specific preferences for HIV related prevention programs. Quantitative surveys, including choices between systematically varied vignettes in the form of a discrete choice experiment conducted with all participating OSC and their caregivers, will elicit the relative acceptability of diverse prevention interventions in the local context. This R01 has significant potential to shift paradigms for the design and implementation of interventions that target the HIV risk and treatment engagement among this most at risk population.